Malbert, C.-H.Chauvin, A.Horowitz, M.Jones, K.L.2025-07-142025-07-142021Diabetes, 2021; 70(1):99-1100012-17971939-327Xhttps://hdl.handle.net/2440/145906The glucose portal sensor informs the brain of changes in glucose inflow through vagal afferents that require an activated glucagon-like peptide 1 receptor (GLP-1r). The GLP-1 system is known to be impaired in insulin-resistant conditions, and we sought to understand the consequences of GLP-1 resistance on glucose portal signaling. GLP-1–dependent portal glucose signaling was identified, in vivo, using a novel ⁶⁸Ga-labeled GLP-1r positron-emitting probe that supplied a quantitative in situ tridimensional representation of the portal sensor with specific reference to the receptor density expressed in binding potential units. It also served as amap for single-neuron electrophysiology driven by an image-based abdominal navigation. We determined that in insulin-resistant animals, portal vagal afferents failed to inhibit their spiking activity during glucose infusion, a GLP-1r–dependent function. This reflected a reduction in portal GLP-1r binding potential, particularly between the splenic vein and the entrance of the liver.We propose that insulin resistance, through a reduction in GLP-1r density, leads to functional portal desensitization with a consequent suppression of vagal sensitivity to portal glucose.en© 2020 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals .org/content/license.glucose portal sensor; brain; glucose inflow; glucagon-like peptide 1 receptor (GLP-1r); single-neuron electrophysiology; insulin-resistantPortal VeinAnimalsSwineSwine, MiniatureInsulin ResistanceObesityInsulinGlucosePositron-Emission TomographyBody CompositionGlucagon-Like Peptide-1 ReceptorInsulin SecretionJournal article10.2337/db20-03612024-05-06551136Malbert, C.-H. [0000-0002-0665-4545]Horowitz, M. [0000-0002-0942-0306]Jones, K.L. [0000-0002-1155-5816]